Chemotherapy and immunotherapy of L1210 leukemic mice with antigenic tumor sublines

Abstract

Tumor cells, treated in vivo with anticancer compounds, may acquire new antigenic specificities in addition to any original antigens associated with parental tumors. Treatment of mice carrying the parental leukemias L1210 Ha or L1210 Cr with leukemia cells antigenically altered by treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (L1210 Ha/DTIC and L1210 Cr/DTIC, respectively) was essentially ineffective in prolonging the life span of the animals. However, synergic therapeutic activity was exhibited by administration of L1210 Ha/DTIC cells plus 1,3-bis(2-chloroethyl)-1-nitrosourea in the treatment of the moderately immunogenic L1210 Ha leukemia and by the combination of L1210 Cr/DTIC cells and lymphocytes immune to L1210 Cr/DTIC administered with 1,3-lymphocytes immune to L1210 Cr/DTIC administered with 1,3-bis(2-chloroethyl)-1-nitrosourea in the treatment of the low immunogenic L1210 Cr leukemia. Early and advanced L1210 Cr-bearing mice showed marked increases in survival time and a significant number of tumor-free survivors on treatment with cyclophosphamide followed by transfer of lymphocytes immune to L1210 Cr/DTIC cells. When parental tumor cells were used as the immunogen, the therapeutic effect was diminished. Thus, in the current investigation, although immunotherapy per se was essentially ineffective, the immunochemotherapeutic modalities used were successful in markedly increasing the survival time of leukemic animals and resulted in an incidence of cures.